This project focuses on the genetic control of graft versus host disease (GVHD) in a mouse model which in many ways reflects the clinical features of GVHD seen in humans. Bone marrow transplantation has become an increasingly utilized treatment modality for aplastic anemia, congenital immunodeficiency syndromes and several forms of leukemia. GVHD is a major post-transplant clinical problem which appears in unpredictable fashion in recipients of HLA matched MLR nonreactive marrow. Hematopoietic cells from C57BL/6 mice (B6) transferred to unirradiated (B6 X D2)Fl recipients induces acute GVHD resulting in pancytopenia, immunosuppression, gastrointestinal lesions and death within several weeks. The existence of an autosomal non-H-2 dominant gene in B6 mice appears to be responsible for this form of GVHD. Confirmation of this hypothesis has come from studies in progeny of [(B6 X D2)Fl X D2] X D2 in which induction of acute GVHD segregates in a fashion consistent with one gene. Twenty-five recombinant inbred (BXD) mouse strains have been examined, but we were not able to establish linkage of this GVH locus with any known loci in B6 mice. Similar linkage studies are being carried out on an autosomal, non-H-2 recessive gene from D2 mice which when present (homozygous) in the donor of hematopoietic cells induces the production of autoantibody to xenotropic retroviruses in the (B6 X D2)F1 recipient. We are currently attempting to determine if this gene is linked to any known locus in D2 mice by examining BXD RI strains. No apparent linkage has yet been established.